High somatostatin receptor expression and efficacy of somatostatin analogues in patients with metastatic Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is an aggressive, high-grade, cutaneous neuroendocrine tumour (NET). PD-1/PD-L1 blocking agents have efficacy in metastatic MCC (mMCC), but half of patients do not derive durable benefit. Somatostatin analogues (SSA) are commonly used to treat low- and moderate-grade NETs that express somatostatin receptors (SSTR).To assess SSTR expression and efficacy of SSA in mMCC, a high-grade NET.In this retrospective study of 40 patients with mMCC, SSTR expression was assessed radiologically by somatostatin receptor scintigraphy (SRS; N=39) and/or immunohistochemically when feasible (N=9). 19 patients (18 had SRS uptake in MCC tumours) were treated with SSA. Disease control (DC) was defined as progression-free survival (PFS) of ≥ 120 days after initiation of SSA.Thirty-three of 39 (85%) patients had some degree (low-52%; moderate-23%; high-10%) of SRS uptake. Of 19 patients treated with SSA, 7 patients had a response-evaluable target lesion; 3 of these 7 (43%) patients experienced DC with a median PFS of 237 days [range 152-358]. 12 of 19 patients did not have a response-evaluable lesion due to antecedent radiation; 5 of these 12 (42%) patients experienced DC (median PFS of 429 days [range 143-1757]). The degree of SSTR expression (by SRS and/or immunohistochemistry) did not correlate significantly with the efficacy endpoints.In contrast to other high-grade NETs, mMCC tumours appear to frequently express SSTR. SSA can lead to clinically meaningful disease control with minimal side effects. SSTR targeting using SSA or other novel approaches should be explored further for mMCC.

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